FACTORS IN ZERO-ORDER RELEASE OF CLONIDINE HYDROCHLORIDE FROM MONOLITHIC POLYDIMETHYLSILOXANE MATRICES

Clonidine hydrochloride loading doses in the 20-40% range are released from monolithic polydimethylsiloxane (PDS) matrices through a self-triggered osmotic pumping mechanism via cracks having formed in the stressed polymer. This mechanism results in zero-order release kinetics when drug particles in the 50-150 .mu.m size range and filler-reinforced PDS are used. Changes in matrix shape (disk vs cylinder) are inconsequential to the zero-order pattern, whereas they do affect release rate. A strong influence of drug loading dose on this rate, as quantified by a highly significant log-log correlation, allows the rate to be modulated over a wide range of pharmacologically interesting values. The zero-order regimen, which lasts several days or months depending on matrix shape and drug load, is preceded by a burst effect and followed by a decline of rate when osmotic pumping ends and the matrix starts shrinking. By this time, around 50% of initial drug load has been released. Release rate is also affected by the pH and buffering competence of the receptor medium.